Production, nano-purification, radiolabeling and biodistribution study of [140Nd] 5,10,15,20-tetraphenylporphyrin complex as a possible imaging agent

[¹⁴⁰Nd] labeled 5,10,15,20-tetraphenylporphyrin ([¹⁴⁰Nd]-TPP) as a tumor–avid complex with a β-emitting radionuclide for evaluating its potential for target tumor therapy is reported. This complex was prepared using freshly prepared [¹⁴⁰Nd] NdCl₃ (purified by amino functionalized MCM-41 nano resin and commercial cation exchanger resins) and 5,10,15,20-tetraphenylporphyrin (H₂TPP).Stability of the complex was investigated in final formulation and human serum for 24 h and the partition coefficient was calculated. The biodistribution of the labeled compound in vital organs of Swiss mice bearing fibro sarcoma tumor was studied using scarification studies and positron emission tomography imaging up to 4 h.     

Preparation and the biodistribution study of [131I]-5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin and 5-(4-aminophenyl)-10,15,20-triphenylporphyrin

[¹³¹I]-5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin and [¹³¹I]-5-(4-aminophenyl)-10,15,20-triphenylporphyrin (¹³¹I-TPPOH and ¹³¹I-TPPNH₂) were prepared and their biodistribution properties were evaluated in normal Kunming (KM) mice and SMMC-7721 tumor-bearing BALB/c mice. The optimized labeling yields were 98 and 96 % for ¹³¹I-TPPOH and ¹³¹I-TPPNH₂, respectively. They were stable in vitro saline and in vivo. Both compounds had a specific affinity to liver and lung, and mainly metabolized through liver. They showed a time-dependent accumulation and retainable characteristics in SMMC-7721 tumor. These results supported their potential value for targeted tumor therapy agents.     

β -Cyclodextrin-Mediated Regioselective Hydrolysis of 5,10,15,20-tetrakis[2,4-bis(pivaloyloxy)phenyl]-21H,23H -porphine

The four peripheral ester moieties of the title compound 5 are regioselectively hydrolyzed under mild conditions in the presence of β -cyclodextrin ( 10 ), providing a new entry to tetraphenylporphyrin derivatives with differently substituted Ph groups in the meso-positions. UV, ¹H-NMR and mass spectroscopy of the inclusion complex 9 of 2,6-O-dimethyl-β-cyclodextrin ( 12 ) and 5 indicate a stoichiometry of 2:1 for 10/5 . Moreover, calculations confirm NOE experiments consistent with the fact that the cyclodextrins 10 and 12 approach the Ph groups of the porphyrin with the small opening of the cavity (primary face).     

Preparation and preliminary evaluation of [<Superscript>67</Superscript>Ga]-tetra phenyl porphyrin complexes as possible imaging agents

[⁶⁷Ga]labeled tetraphenyl porphyrin ([⁶⁷Ga]-TPP) was prepared using freshly prepared [⁶⁷Ga]GaCl₃ and tetraphenyl porphyrin (TPPH₂) for 30–60 min at 25 °C (radiochemical purity: >97 ± 1% ITLC, >98 ± 0.5% HPLC, specific activity: 13–14 GBq/mmol). Stability of the complex was checked in final formulation and human serum for 24 h. The partition coefficient was calculated for the compound (log P 1.89). The biodistribution of the labeled compound in vital organs of wild-type rats was studied using scarification studies and SPECT imaging up to 24 h. A detailed comparative pharmacokinetic study performed for ⁶⁷Ga cation and [⁶⁷Ga]-TPP. The complex is mostly washed out from the circulation through kidneys and can be an interesting tumor imaging/targeting agent due to low liver uptake and rapid excretion through the urinary tract.     

5,10,15,20-Tetrakis[4'-(terpyridinyl)phenyl]porphyrin and its RuII complexes: synthesis, photovoltaic properties, and self-assembled morphology

A novel tetrakis(terpyridinyl)porphyrin derivative and its Ru(II) complexes were efficiently synthesized using microwave enhanced synthesis and shown to possess photovoltaic properties. Transmission electron microscopy and selected area electron diffraction were used to investigate its nanowire self-assembly.     

Oxidation of azo dye Orange II with hydrogen peroxide catalyzed by 5,10,15,20-tetrakis[4-(diethylmethylammonio)phenyl]porphyrinato-cobalt(II)tetraiodide in aqueous solution

The catalytic oxidation of the azo dye Orange II by hydrogen peroxide in aqueous solution has been investigated using 5,10,15,20-tetrakis-[4-(diethylmethylammonio)phenyl]porphyrinato-cobalt(II) tetra iodide 1as catalyst. The oxidation reaction was followed by recording the UV–vis spectra of the reaction mixture with time at λ_max = 485 nm. The factors that may influence the oxidation of Orange II, such as the effect of reaction temperature, concentration of catalyst, hydrogen peroxide and orange II have been studied. The results of total organic carbon analysis showed 52% of dye mineralization under mild reaction conditions. Residual organic compounds in the reaction mixture were identified by using Gas chromatography-mass spectrometry. The decolorization rate and mineralization of the dye has been found to increase with increase of catalyst concentration and reaction temperature. The rate of dye oxidation decreased with increasing the concentration of dye, H₂O₂ and at higher pH than 9. Radical scavenging measurement indicated that decolorization of Orange II by H₂O₂/cobalt (II) porphyrin complex 1 involved the formation of hydroxyl radicals as the active species.     

5,10,15,20-四{对[3,5-二-(烷氧基)苯甲酰胺基]苯基}卟啉及其锌配合物的合成表征

设计合成了5种未见文献报道的5,10,15,20-四{对[3,5-二-(烷氧基)苯甲酰胺基]苯基}卟啉及其锌金属配合物,并用IR,UV-Vis,1H NMR,元素分析以及XPS对其组成和结构进行了表征,研究了这10种酰胺基系列卟啉化合物的拉曼光谱和荧光光谱的变化.结果显示链长对荧光和拉曼光谱没有明显影响,其取代基效应基本相同,配体的荧光强度强于锌配合物的荧光强度.在拉曼光谱中,由于卟啉分子平面的对称性由D2h变为D4h群及其锌离子d轨道的电子效应,卟啉配体和锌配合物之间的拉曼光谱有很大差别.     

Proton transfer reactions from N-H acid [5,10,15,20-tetrakis(pentafluorophenyl)-21-H, 23-H-porphyrin] to strong bases in acetonitrile

Deprotonation of 5,10,15,20-tetrakis(pentafluorophenyl)-21-H, 23-H-porphyrin (PhF₅PorH₂) by various bases has been studied by ¹H NMR and kinetic methods. The kinetic parameters in acetonitrile were defined for proton transfer reactions yielding [NH]⁺ protonated bases and [NHN]⁻ anions with intramolecular hydrogen-bonded chains.     

四(4-磺酸基苯基)卟啉锰钠盐-NO配合物的合成及NO释放效能和 生物学活性研究

合成、表征了一种新型的NO供体化合物meso-5,10,15,20-四(4-磺酸基苯基)卟啉锰钠盐—NO配合物(TPPSNa-Mn-NO), 并初步研究其药理学作用. 采用重氮化偶合反应检测TPPSNa-Mn-NO体外NO的释放效果. 观察TPPSNa-Mn-NO对家兔离体胸主动脉环的舒张作用和对于大鼠收缩压、舒张压及心率的影响. TPPSNa-Mn-NO的体外NO释放效率约为70.86%, 该化合物可以使30 mmol&#8226;L－1甲氧胺引起家兔离体胸主动脉收缩的量效关系曲线非平行右移, 最大反应(Emax)压降低约30.2%, 静脉给药后实验组大鼠血压第5 min时开始下降, 并持续缓慢降低, 给药后30 min下降幅度达最大, 而后缓慢回升, 给药后120 min时接近用药前水平且仍低于用药前水平. 药物对大鼠心率无显著影响. TPPSNa-Mn-NO具有缓慢持久降压的药理作用, 且不影响其他重要的生命指标, 有望成为长效降压药理想的候选化合物.     

Radio labeling,quality control and biodistribution of <Superscript>99m</Superscript>Tc-cefotaxime as an infection imaging agent

Cefotaxime, a cephalosporin antibiotic, used to treat bacterial infections was investigated to label with ^99mTc. Labeling was performed using sodium dithionite as a reducing agent at 100 °C for 10 min and radiochemical analysis involved ITLC and HPLC methods. The stability of labeled antibiotic was checked in the presence of human serum at 37 °C up to 24 h. The maximum radiolabeling yield was 92 ± 2%. Bacterial binding assay was performed with S. aureus and the in vivo distribution was studied in mice. Images showed minimal accumulation in non-target tissues, with an average target/non-target ratio of 2.89 ± 0.58.     

2,5-di-[2-(3,5-bis(2-pyridylmethyl)amine -4-hydroxy-phenyl) ethylene] pyrazine zinc complex as fluorescent probe for labeling proteins

The binding characteristics between 2,5-di-[2-(3,5-bis(2-pyridylmethyl)amine -4-hydroxy-phenyl) ethylene] pyrazine (1) or its complex (1-Zn) and serum albumins were studied by fluorescence spectroscopy in pH 7.4 aqueous solution. 1-Zn emitted weak fluorescence at 580 nm in a pH 7.4 Tris-HCl buffer solution when excited at 435 nm, however, the fluorescence intensity increased upon addition of serum albumins with the blue shift of emission peak to 524 nm. The binding constants were estimated as 8.40 x 10(7) and 3.03 x 10(6)mol(-1)L for bovine serum albumin (BSA) and human serum albumin (HSA) respectively, and the number of binding sites was 1 for each. The quenching mechanism of fluorescence of serum albumins by 1-Zn was considered as a static quenching process. The binding distance between 1-Zn and serum albumins and the energy transfer efficiency were obtained based on the theory of F?rester spectroscopy energy transfer. The effect of 1-Zn on the conformation of serum albumins was further analyzed using synchronous fluorescence spectrometry. The experiment results clearly showed that 1-Zn is a highly sensitive protein sensor.     

Design, Synthesis and Biological Activity of Substituted-N-[4-（substituted-phenylsulfamoyl）phenyl]benzamide as Potential AHAS Inhibitors

Acetohydroxyacid synthase (AHAS) is an ideal target for the design of environmental benign herbicides, because it catalyzes the first step in the biosynthesis of branched chain amino acids, which does not exist in mammal bodies1-4. Typical AHAS inhibitors…     

Preparation, crystal structure, and spectroscopic, chemical, and electrochemical properties of (2E,4E)-4-[4-(dimethylamino)phenyl]-1-(3-guaiazulenyl)-1,3-butadiene compared with those of (E)-2-[4-(dimethylamino)phenyl]-1-(3-guaiazulenyl)ethylene

Wittig reaction of 3-[4-(dimethylamino)phenyl]propanal (5) with (3-guaiazulenylmethyl)triphenylphosphonium bromide (4) in ethanol containing NaOEt at 25 °C for 24 h under argon gives the title (2E,4E)-1,3-butadiene derivative 6E in 19% isolated yield. Spectroscopic properties, crystal structure, and electrochemical behavior of the obtained new extended π-electron system 6E, compared with those of the previously reported (E)-2-[4-(dimethylamino)phenyl]-1-(3-guaiazulenyl)ethylene (12), are documented. Furthermore, reaction of 6E with 1,1,2,2-tetracyanoethylene (TCNE) in benzene at 25 °C for 24 h under argon affords a new Diels-Alder adduct 8 in 59% isolated yield. Along with spectroscopic properties of the [π4+π2] cycloaddition product 8, the crystal structure, possessing a cis-3,6-substituted 1,1,2,2-tetracyano-4-cyclohexene unit, is shown. Moreover, reaction of 6E with (E)-1,2-dicyanoethylene (DCNE) under the same reaction conditions as the above gives no product; however, this reaction in p-xylene at reflux temperature (138 °C) for four days under argon affords a new Diels-Alder adduct 9 in 54% isolated yield. Although reaction of 6E with DCNE in toluene at reflux temperature (110 °C) for four days under argon provides 9 very slightly, reaction of 6E with dimethyl acetylenedicarboxylate (DMAD) in toluene at reflux temperature for two days under argon yields a new Diels-Alder adduct 10, in 58% isolated yield, which upon oxidation with MnO₂ in CH₂Cl₂ at 25 °C for 1 h gives 11, converting a (CH₃)₂N-4″ into CH₃NH-4″ group, in 37% isolated yield. The crystal structure of 11 supports the molecular structure 10 possessing a partial structure cis-3,6-substituted 1,2-dimethoxycarbonyl-1,4-cyclohexadiene. The title basic studies on the above are reported in detail.     

5,10,15,20-tetrakis(N-methyl-4-pyridyl)-21H,23H-porphine (TMPyP) as a sensitizer for singlet oxygen imaging in cells: characterizing the irradiation-dependent behavior of TMPyP in a single cell

Singlet molecular oxygen, a1Delta(g), can be detected from a single cell by its weak 1270 nm phosphorescence (a1Delta(g)-->X3Sigma(g)-) upon irradiation of the photosensitizer 5,10,15,20-tetrakis(N-methyl-4-pyridyl)-21H,23H-porphine (TMPyP) incorporated into the cell. The behavior of this sensitizer in a cell, and hence the behavior of the associated singlet oxygen phosphorescence signal, depends on the conditions under which the sample is exposed to light. Upon irradiation of a neuron freshly incubated with TMPyP, the intensity of TMPyP fluorescence initially increases and there is a concomitant increase in the singlet oxygen phosphorescence intensity from the cell. These results appear to reflect a photoinduced release of TMPyP bound to DNA in the nucleus of the cell, where TMPyP tends to localize, and the subsequent relocalization of TMPyP to a different microenvironment in the cell. Upon prolonged irradiation of the cell, TMPyP photobleaches and there is a corresponding decrease in the singlet oxygen phosphorescence intensity from the cell. The data reported herein provide insight into key factors that can influence photosensitized singlet oxygen experiments performed on biological samples.     

Practical synthesis of a 1beta-methylcarbapenem, J-111,225, using 4-mercapto-2-[4-(N-methylaminomethyl)phenyl]pyrrolidine as a precursor

An effective and practical procedure for the synthesis of J-111,225 (1), a new 1beta-methylcarbapenem, was developed using 4-mercapto-2-14-(N-methylaminomethyl)phenyl]pyrrolidine (2a) as a precursor. The coupling reaction of 2a with p-nitrobenzyl (PNB)-protected 1beta-methylcarbapenem enolphosphate 3a and successive removal of PNB group afforded J-111,225 (1) in significantly increased yield compared to the ordinary procedure using a C-2 side-chain thiol with amino-protective groups.